MetaCyc Pathway: methylglyoxal degradation I
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: methylglyoxal degradation I

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationAldehyde Degradation
DetoxificationMethylglyoxal Detoxification

Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655, Homo sapiens, Pseudomonas putida, Saccharomyces cerevisiae

Expected Taxonomic Range: Bacteria , Fungi, Metazoa

General Background

Methylglyoxal is produced in small amounts during glycolysis (via glycerone phosphate), fatty acid metabolism (via acetone), and protein metabolism (via aminoacetone). Methylglyoxal is highly toxic, most likely as a result of its interaction with protein side chains (see [Kalapos99] for a review). There are several pathways for the detoxification of methylglyoxal, based on different enzymes that are able to convert methylglyoxal to less toxic compounds. These enzymes include glyoxalase enzymes, methylglyoxal reductases, aldose reductases, aldehyde reductases and methylglyoxal dehydrogenases.

About This Pathway

The glyoxalase system is probably the most common pathway that catalyzes the conversion of methylglyoxal to a less toxic product. In this pathway, methylglyoxal is converted to (R)-lactate via the intermediate (R)-S-lactoylglutathione by 2 enzymes:

glyoxalase I isomerizes the hemithioacetal that is formed non-enzymatically from methylglyoxal and glutathione to (R)-S-lactoylglutathione. glyoxalase II hydrolyzes the thioester to (R)-lactate regenerating the glutathione in the process.

The fate of (R)-lactate has been less well characterized. The most likely scenario is its conversion to pyruvate by the action of D-lactate dehydrogenase, a flavoprotein specific to the D-form of lactate [Olson79, Flick02].

The pathway is ubiquitous in biological life, taking place in the cytosol of prokaryotes and the mitochondria of eukaryotes [Ewaschuk05].

Superpathways: superpathway of methylglyoxal degradation

Variants: methylglyoxal degradation II, methylglyoxal degradation III, methylglyoxal degradation IV, methylglyoxal degradation V, methylglyoxal degradation VI, methylglyoxal degradation VII, methylglyoxal degradation VIII

Unification Links: EcoCyc:PWY-5386

Created 24-Oct-2006 by Caspi R, SRI International


Ewaschuk05: Ewaschuk JB, Naylor JM, Zello GA (2005). "D-lactate in human and ruminant metabolism." J Nutr 135(7);1619-25. PMID: 15987839

Flick02: Flick MJ, Konieczny SF (2002). "Identification of putative mammalian D-lactate dehydrogenase enzymes." Biochem Biophys Res Commun 295(4);910-6. PMID: 12127981

Kalapos99: Kalapos MP (1999). "Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications." Toxicol Lett 110(3);145-75. PMID: 10597025

Olson79: Olson ST, Massey V (1979). "Purification and properties of the flavoenzyme D-lactate dehydrogenase from Megasphaera elsdenii." Biochemistry 18(21);4714-24. PMID: 497162

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Barnes70: Barnes EM, Kaback HR (1970). "Beta-galactoside transport in bacterial membrane preparations: energy coupling via membrane-bounded D-lactic dehydrogenase." Proc Natl Acad Sci U S A 66(4);1190-8. PMID: 4394455

Barnes71: Barnes EM, Kaback HR (1971). "Mechanisms of active transport in isolated membrane vesicles. I. The site of energy coupling between D-lactic dehydrogenase and beta-galactoside transport in Escherichia coli membrane vesicles." J Biol Chem 1971;246(17);5518-22. PMID: 4330922

Bito97: Bito A, Haider M, Hadler I, Breitenbach M (1997). "Identification and phenotypic analysis of two glyoxalase II encoding genes from Saccharomyces cerevisiae, GLO2 and GLO4, and intracellular localization of the corresponding proteins." J Biol Chem 272(34);21509-19. PMID: 9261170

Bito99: Bito A, Haider M, Briza P, Strasser P, Breitenbach M (1999). "Heterologous expression, purification, and kinetic comparison of the cytoplasmic and mitochondrial glyoxalase II enzymes, Glo2p and Glo4p, from Saccharomyces cerevisiae." Protein Expr Purif 17(3);456-64. PMID: 10600466

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Campbell84: Campbell HD, Rogers BL, Young IG (1984). "Nucleotide sequence of the respiratory D-lactate dehydrogenase gene of Escherichia coli." Eur J Biochem 144(2);367-73. PMID: 6386470

CamposBermudez10a: Campos-Bermudez VA, Gonzalez JM, Tierney DL, Vila AJ (2010). "Spectroscopic signature of a ubiquitous metal binding site in the metallo-β-lactamase superfamily." J Biol Inorg Chem 15(8);1209-18. PMID: 20535505

Clugston04: Clugston SL, Yajima R, Honek JF (2004). "Investigation of metal binding and activation of Escherichia coli glyoxalase I: kinetic, thermodynamic and mutagenesis studies." Biochem J 377(Pt 2);309-16. PMID: 14556652

Clugston98: Clugston SL, Barnard JF, Kinach R, Miedema D, Ruman R, Daub E, Honek JF (1998). "Overproduction and characterization of a dimeric non-zinc glyoxalase I from Escherichia coli: evidence for optimal activation by nickel ions." Biochemistry 1998;37(24);8754-63. PMID: 9628737

Davidson00: Davidson G, Clugston SL, Honek JF, Maroney MJ (2000). "XAS investigation of the nickel active site structure in Escherichia coli glyoxalase I." Inorg Chem 39(14);2962-3. PMID: 11196887

Davidson01: Davidson G, Clugston SL, Honek JF, Maroney MJ (2001). "An XAS investigation of product and inhibitor complexes of Ni-containing GlxI from Escherichia coli: mechanistic implications." Biochemistry 40(15);4569-82. PMID: 11294624

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dym00: Dym O, Pratt EA, Ho C, Eisenberg D (2000). "The crystal structure of D-lactate dehydrogenase, a peripheral membrane respiratory enzyme." Proc Natl Acad Sci U S A 97(17);9413-8. PMID: 10944213

Frickel01: Frickel EM, Jemth P, Widersten M, Mannervik B (2001). "Yeast glyoxalase I is a monomeric enzyme with two active sites." J Biol Chem 276(3);1845-9. PMID: 11050082

Fung79: Fung LW, Pratt EA, Ho C (1979). "Biochemical and biophysical studies on the interaction of a membrane-bound enzyme, D-lactate dehydrogenase from Escherichia coli, with phospholipids." Biochemistry 1979;18(2);317-24. PMID: 369600

Futai73: Futai M (1973). "Membrane D-lactate dehydrogenase from Escherichia coli. Purification and properties." Biochemistry 12(13);2468-74. PMID: 4575624

GeorgeNasciment76: George-Nascimento C, Wakil SJ, Short SA, Kaback HR (1976). "Effect of lipids on the reconstitution of D-lactate oxidase in Escherichia coli membrane vesicles." J Biol Chem 251(21);6662-6. PMID: 789373

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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